Can zoledronic acid reduce the risk of cage subsidence after oblique lumbar interbody fusion combined with bilateral pedicle screw fixation in the elderly population? A retrospective study

Background The objective of this study was to evaluate the potential of zoledronic acid for reducing the incidence of cage subsidence and enhancing interbody fusion rates following oblique lumbar interbody fusion (OLIF) surgery, particularly as the first reported evidence of the role of zoledronic acid combined with OLIF. Methods A retrospective analysis was conducted on data from 108 elderly patients treated for degenerative lumbar diseases using OLIF combined with bilateral pedicle screw fixation from January 2018 to December 2021. Patients were divided into the zoledronic acid (ZOL) group (43 patients, 67 surgical segments) and the control group (65 patients, 86 surgical segments). A comparative analysis of the radiographic and clinical outcomes between the groups was performed, employing univariate and multivariate regression analyses to explore the relationships between cage subsidence and the independent variables. Results Radiographic outcomes, including anterior height, posterior height, disc height, coronal disc angle, foraminal height, and lumbar lordosis, were not significantly different between the two groups. Similarly, no statistically significant differences were noted in the back visual analog scale (VAS) scores and Oswestry Disability Index (ODI) scores between the groups. However, at the 1-year follow-up, the leg VAS score was lower in the ZOL group than in the control group (P = 0.028). The ZOL group demonstrated a notably lower cage subsidence rate (20.9%) than did the control group (43.0%) (P < 0.001). There was no significant difference in the interbody fusion rate between the ZOL group (93.0%) and the control group (90.8%). Non-use of zoledronic acid emerged as an independent risk factor for cage subsidence (OR = 6.047, P = 0.003), along with lower bone mineral density, lower postoperative anterior height, and concave endplate morphology. The model exhibited robust discriminative performance, with an area under the curve (AUC) of 0.872. Conclusion The administration of zoledronic acid mitigates the risk of cage subsidence following OLIF combined with bilateral pedicle screw fixation in elderly patients; however, it does not improve the interbody fusion rate. Supplementary Information The online version contains supplementary material available at 10.1186/s13018-024-04828-3.


Comment: Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?
Response: I appreciate the editor's question regarding the appropriateness of our study design and the support for our conclusions.In this study, our study population comprised patients aged over 50 with degenerative lumbar diseases treated with OLIF combined with posterior fixation, grouped based on postoperative zoledronic acid use.Although we did not match based on factors such as age and preoperative BMD, baseline characteristics including age, gender, BMD, surgical segments, and number of surgical segments showed no statistically significant differences between the Zol group and the control group, indicating comparability between the two groups.Of course, the editor's suggestions also provide direction for our future research endeavors.
The conclusions drawn from our study are supported by the evidence presented.We found a significant reduction in cage subsidence rates in the zoledronic acid group compared to the control group, highlighting the potential of zoledronic acid in mitigating this complication following OLIF surgery.However, we also acknowledge that the administration of zoledronic acid did not result in a significant increase in interbody fusion rates.In conclusion, while our study provides valuable insights into the role of zoledronic acid in OLIF surgery, we recognize the limitations inherent in our retrospective design and the need for further research to validate our findings.
Change: (Page 22, Line 418-420) Although matching based on factors such as age and preoperative BMD was not conducted, baseline characteristics were comparable between the two groups.

Comment:
The use of the 2mm threshold to mark subsidence is interesting.However other metrics could be employed to further investigate the severity of subsidence.
Response: I appreciate the editor's observation regarding the threshold used to define subsidence in our study.The choice of a 2mm threshold for defining subsidence is one approach among several possible metrics, as acknowledged.While our study employed this threshold for consistency and comparability with existing literature[1-3], we recognize that alternative metrics could offer additional insights into the severity of subsidence.Notably, previous literature has reported grading the degree of cage subsidence based on the reduction in disc height (DH) postoperatively, with different grades representing varying degrees of disc height loss [4,5].
Following the editor's suggestion and in accordance with previous literature, an additional analysis comparing the severity of cage subsidence between the two groups was conducted (Supplementary Table 2).The results indicated no statistically significant differences between the groups, and none of the patients experienced severe cage subsidence (graded as Grade 2 and 3).This observation may be attributed to our study population, consisting of patients treated with OLIF combined with bilateral pedicle screw fixation, which may substantially reduce the risk of severe cage subsidence post-OLIF.However, further validation in future studies is warranted.

Comment:
Maybe the inclusion of a survival analysis to assess whether in time each group presented with subsidence would be nice.
Response: I appreciate the editor's suggestion regarding the potential inclusion of a survival analysis to assess the timing of subsidence occurrence in each group.Survival analysis could indeed offer valuable insights into the temporal patterns of subsidence development following OLIF surgery.We acknowledge the merit of this approach in providing a more nuanced understanding of the dynamics of cage subsidence over time.Incorporating survival analysis could enhance our ability to discern differences in the timing and frequency of subsidence events between groups, thereby contributing to a deeper comprehension of this postoperative complication.However, in this retrospective study, we only assessed cage subsidence at 1 year postoperatively, the data on cage subsidence evaluations at 1 month, 3 months, or 6 months postoperatively were not available.We will carefully consider the feasibility and potential benefits of incorporating survival analysis into our future research endeavors.Thank you for highlighting this suggestion, and we will explore its applicability in further enhancing the robustness of our study findings.

Comment:
Further investigating the evolution of the subsidence could be interesting in the present study (Ex: patient needed reoperation, or, delta subsidence from each time point to asses if the endplate damage is increasing or decreasing).
Response: I appreciate the editor's insightful suggestion to further investigate the evolution of subsidence in our study.Assessing factors such as the need for reoperation and analyzing the change in subsidence over time, specifically examining delta subsidence at different time points, could indeed provide valuable insights into the progression of endplate damage following OLIF surgery.
These additional analyses could offer a more comprehensive understanding of the long-term implications of cage subsidence and its impact on clinical outcomes.We will carefully consider incorporating these aspects into our future research endeavors to enrich the depth of our findings.
Thank you for highlighting these avenues for further exploration, and we will explore their feasibility in enhancing the comprehensiveness of our study.

Table 2 . Comparison of the severity of cage subsidence between the two groups.
Future research exploring alternative thresholds or complementary measures to evaluate the extent and impact of subsidence would be beneficial in enhancing our understanding of this complication following OLIF surgery.Thank you for highlighting this aspect, and we will consider incorporating alternative metrics in future studies to provide a more comprehensive assessment of subsidence severity.